IMB 1800 Programs for Data processing at the Accelerators of the Central Bureau for Nuclear Measurements. Part 3: Programs for Interactive Data Reduction. EUR 4404.

<p>A, miR393 and <i>DlCHS</i>; B, miR393 and <i>DlCHI</i>; C, miR393 and <i>DlFLS</i>; D, miR393 and <i>DlF3′H</i>; E, miR393 and <i>DlDFR</i>; F, miR393 and <i>DlLAR</i>; G, miR393 and its target gene <i>DlTIR1-3</i>.</p

Physiologically based pharmacokinetic model of docetaxel and interspecies scaling: comparison of simple injection with folate receptor-targeting amphiphilic copolymer-modified liposomes

<p>1. To compare the disposition of docetaxel (DTX) in male/female rats after intravenous administration of simple injection and folate-poly(PEG-cyanoacrylate-co-cholesteryl cyanoacrylate)-modified liposomes utilising a physiologically based pharmacokinetic (PBPK) modelling method, and extrapolate this model to mice and humans by taking into account the interspecies differences in physiological- and chemical-specific parameters.</p> <p>2. Four structural models for single organs were evaluated, and the whole-body PBPK model included artery, vein, lung, brain, heart, spleen, liver, gastrointestinal tract, kidney, muscle and remainder compartment.</p> <p>3. Rats following modified liposomes administration were characterised by significant decrease in the partition coefficients for brain, spleen, liver and remainder compartment. The blood-to-plasma partition coefficient also decreased significantly, while a marked rise of partition coefficients for lung, kidney and muscle was revealed. Partition coefficient for heart was approximately 1.3-fold higher in females than males, while the decrease of intestinal clearance was revealed in females compared to males. The final model successfully characterised the time course of DTX in rats, mice and humans.</p> <p>4. This PBPK model is beneficial to the prediction of the effects of DTX in different species. It also represented a platform to encompass both formulation- and sex-related effects on DTX disposition and elimination in the future.</p

Table1_A mosaic mutation in the CLCNKB gene causing Bartter syndrome: A case report.xlsx

BackgroundType III Bartter syndrome (BS) is an autosomal recessive disease caused by mutations in the CLCNKB (chloride voltage-gated channel Kb) gene that encodes CLC-Kb. CLC-Kb is mainly located in the thick ascending limb of Henle's loop and regulates chloride efflux from tubular epithelial cells to the interstitium. Type III BS is characterized by metabolic alkalosis, renal salt wasting, hyperreninemia, and hyperaldosteronism with normal blood pressure.Case presentationWe reported the case of a 3-day-old girl whose initial symptom we diagnosed as jaundice, but we accidentally found metabolic alkalosis. She showed recurrent metabolic alkalosis, hypokalemia, and hypochloremia and also had hyperreninemia and hyperaldosteronism with normal blood pressure. Both oral potassium supplements and potassium infusion therapy were unable to entirely restore the electrolyte imbalance. She was suspected of Bartter syndrome and genetic tests were performed on her and her parents. Next-generation sequencing identified CLCNKB gene mutation including heterozygous mutation c.1257delC (p.M421Cfs*58) and a low-level mutation c.595G > T (p.E199*); both mutations were also verified in the parents.ConclusionWe reported the case of a classic Bartter syndrome in a newborn with a heterozygous frameshift mutation and a mosaic non-sense mutation in the CLCNKB gene.</p

Construction of Electrochemical Chiral Interfaces with Integrated Polysaccharides via Amidation

Polysaccharides of sodium carboxymethyl cellulose (CMC) and chitosan (CS) were integrated together via amidation reactions between the carboxyl groups on sodium CMC and the amino groups on CS. Compared with individual sodium CMC and CS, the integrated polysaccharides with a mass ratio of 1:1, CMC–CS (1:1), exhibited a three-dimensional (3D) porous network structure, resulting in a significantly enhanced hydrophility due to the exposed polar functional groups in the CMC–CS (1:1). Chiral interfaces were constructed with the integrated polysaccharides and used for electrochemical enantiorecognition of tryptophan (Trp) isomers. The CMC–CS (1:1) chiral interfaces exhibited excellent selectivity toward the Trp isomers owing to the highly hydrophilic feature of CMC–CS (1:1) and the different steric hindrance during the formation of H bonds between Trp isomers and CMC–CS (1:1). Also, the optimization in the preparation of integrated polysaccharides such as mass ratio and combination mode (amidation or electrostatic interactions) was investigated. The CMC–CS (1:1) presented the ability of determining the percentage of d-Trp in racemic mixtures, and thus, the proposed electrochemical chiral interfaces could be regarded as a potential biosensing platform for enantiorecognition of chiral compounds

Table_1_Effects of three different probiotics of Tibetan sheep origin and their complex probiotics on intestinal damage, immunity, and immune signaling pathways of mice infected with Clostridium perfringens type C.DOCX

Tibetan sheep have unique intestinal microorganisms in their intestines that are adapted to the highland alpine and anoxic environment. To further clarify the probiotic properties of Tibetan sheep-derived probiotics, we selected three Tibetan sheep-derived probiotic isolates (Enterococcus faecalis EF1-mh, Bacillus subtilis BS1-ql, and Lactobacillus sakei LS-ql) to investigate the protective mechanisms of monocultures and their complex strains against Clostridium perfringens type C infection in mice. We established a model of C. perfringens type C infection and used histology and molecular biology to analyze the effects and mechanisms of different probiotic treatments on mice after C. perfringens type C infection. After supplementation with either probiotics or complex probiotics, mice were improved in terms of weight reduction and reduced the levels of cytokines in serum and increased the levels of intestinal sIgA, and supplementation with complex probiotics was effective. In addition, both probiotic and complex probiotic supplementation effectively improved the damage of intestinal mucosa and spleen tissue. The relative expressions of Muc 2, Claudin-1, and Occludin genes were increased in the ileum. The three probiotics and the compound probiotics treatment significantly reduced the relative mRNA expression of toll-like/MyD88/NF-κB/MAPK. The effect of probiotic treatment was similar to the results of engramycin treatment, but the effect of engramycin treatment on intestinal sIgA was not significant. Our results clarify the immunomodulatory effects of the three probiotic isolates and the complex probiotics on C. perfringens infection, and the repair of the intestinal mucosal barrier.</p

Representative positive base peak intensity (BPI) chromatograms of urine samples at 336 h post-treatment:

<p>(A) GF-treated group (B) Healthy control group <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067451#pone.0067451-Geng1" target="_blank">[19]</a>.</p

LFDR plot for simulation data of the Case group and the Control group.

<p>Integers in red indicate potential biomarkers and integers in black indicate other markers. 0.05 (dash line) is treated as the threshold for potential biomarkers identification. The integers below the dash line are identified as potential biomarkers.</p

The PCA score plot and corresponding loading plot for the simulation data:

<p>(A) The score plot showing the separation between the Case group(X) and the Control group (o) (B) Loading plot for potential biomarker recognition. Metabolites 4, 6, 9, 11, and 12 are identified as potential biomarkers. Integers in red indicate biomarkers and integers in black indicate other markers.</p

Biomarkers of hepatotoxicity induced by GF treatment.

*<p>Metabolite identified with database and commercially available references.</p>**<p>Metabolite identified with MS/MS fragment in the database and literature.</p

LFDR plot for the metabolic profiles of the GF-treated and healthy control groups.

<p>(A) LFDR from 0 to 1 (B) LFDR form 0 to 0.20. The metabolites marked by blue X with retention time-m/z pair below the dash line are identified as the potential biomarkers. 0.05 (dash line) is treated as the threshold for potential biomarkers identification.</p